title: Serum proteome predicts virological response in chronic hepatitis C genotype 1b patients treated with pegylated interferon plus ribavirin.
abstract: OBJECTIVE
  Whether serum proteome changes can predict treatment response in chronic hepatitis C remains unclear. We investigated the association between serum proteome changes and virological responses in chronic hepatitis C virus genotype 1b (HCV-1b) patients treated with pegylated interferon (PegIFN) plus ribavirin (RBV).
  
  
  METHODS
  One hundred and thirty-six HCV-1b patients who had completed a course of PegIFN plus RBV for 24 weeks, had a 24-week follow-up, and had pretreatment serum available were enrolled. These patients were divided into training and validation groups. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) for peptide profiling and ClinPro Tools version 2.0 bioinformatics software for data analysis.
  
  
  RESULTS
  Seventy-four patients (54%) had a sustained virological response (SVR), whereas 62 did not. We identified three protein peaks in pretreatment sera where the expression levels significantly differed between SVR and non-SVR (p < 0.05). Using the class prediction tool composed of the three protein peaks, we were able to correctly predict SVR in 95% of validation group patients with sensitivity = 95%, specificity = 56.3%, positive predictive value = 73.1%, and negative predictive value = 90%. We also identified a set of 20 protein peaks where the expression levels significantly differed in pretreatment sera between patients with nonresponse (NR) and virological response (SVR plus relapse; p < 0.05). Using the class prediction tool composed of these 20 protein peaks, we were able to correctly predict virological NR in 82% of validation group patients with sensitivity = 100%, specificity = 82%, positive predictive value = 92.6%, and negative predictive value = 100%.
  
  
  CONCLUSIONS
  Pretreatment serum proteome allows prediction of SVR and NR to PegIFN plus RBV treatment in HCV-1b patients.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Yen
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jyh-Chwan
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kwong-Ming
authors.initials: KM
authors.lastname: Kee
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Clinical Genomic and Proteomic Core Laboratory, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: cchsiao@mail.cgu.edu.tw.
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Hsiao
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Chinese Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: chmolee@ms15.hinet.net.
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015999:Multivariate Analysis; D020543:Proteome / Q000032:analysis*; D012254:Ribavirin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013624:Taiwan; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D020543:Proteome; D012254:Ribavirin
keywords: hepatitis C virus genotype 1; serum proteome; sustained virological response